Ischemic Neuronal Apoptosis: A View Based on Free Radical-Induced DNA Damage and Repair

1998 ◽  
Vol 4 (2) ◽  
pp. 88-95 ◽  
Author(s):  
Arif Y. Shaikh ◽  
Uthayshanker R. Ezekiel ◽  
Philip K. Liu ◽  
Chung Y. Hsu
Keyword(s):  
Dna Damage ◽  
Free Radicals ◽  
Free Radical ◽  
Base Excision Repair ◽  
Neuronal Apoptosis ◽  
Excision Repair ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Dna Damage And Repair ◽  
Base Excision

Neurons are different from other cells in that they are postmitotic and not replaced after they are lost. The CNS is thus particularly vulnerable to neuronal cell loss from various causes, including ischemic injury. Recent observations show that apoptosis is a common feature in neurons dying of ischemic injury. Free radicals have been implicated in the pathogenesis of ischemic brain injury. Reperfusion after cerebral ischemia is accompanied by excessive free radical formation. Many of these free radicals are reactive oxygen species and cause oxidative damage to DNA. The base-excision repair pathway is believed to repair oxidative DNA damage in the brain after ischemia-reperfusion. We review recent laboratory findings that provide evidence of free radical-induced DNA damage and repair after ischemic injury. The polymerase responsible for replication during base-excision repair, DNA polymerase-β, lacks proofreading activity and is considered error prone. This may lead to the accumulation of DNA damage and genomic instability, probable causes of accelerated neuronal aging. A number of DNA repair genes, including ataxia teleangiectasia, p53, and poly(ADP-ribose) polymerase, are activated after DNA damage. The pathogenetic roles of these genes in ischemia-induced neuronal apoptosis are under active investigation. NEUROSCIENTIST 4:88-95, 1998

scholarly journals Mechanistic Insight into DNA Damage and Repair in Ischemic Stroke: Exploiting the Base Excision Repair Pathway as a Model of Neuroprotection

2011 ◽  
Vol 14 (10) ◽  
pp. 1905-1918 ◽  
Author(s):  
Peiying Li ◽  
Xiaoming Hu ◽  
Yu Gan ◽  
Yanqin Gao ◽  
Weimin Liang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ischemic Stroke ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Pathway ◽  
Dna Damage And Repair ◽  
Base Excision Repair Pathway ◽  
Mechanistic Insight ◽  
Base Excision ◽  
Insight Into

scholarly journals Genetic Analysis of Transcription-Associated Mutation in Saccharomyces cerevisiae

Genetics ◽  
2000 ◽  
Vol 154 (1) ◽  
pp. 109-120 ◽  
Author(s):  
Natalie J Morey ◽  
Christopher N Greene ◽  
Sue Jinks-Robertson
Keyword(s):  
Dna Damage ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Mutation Rates ◽  
Base Pairs ◽  
Genetic Studies ◽  
Dna Damage And Repair ◽  
Nucleotide Excision ◽  
Translesion Bypass ◽  
Base Excision

Abstract High levels of transcription are associated with elevated mutation rates in yeast, a phenomenon referred to as transcription-associated mutation (TAM). The transcription-associated increase in mutation rates was previously shown to be partially dependent on the Rev3p translesion bypass pathway, thus implicating DNA damage in TAM. In this study, we use reversion of a pGAL-driven lys2ΔBgl allele to further examine the genetic requirements of TAM. We find that TAM is increased by disruption of the nucleotide excision repair or recombination pathways. In contrast, elimination of base excision repair components has only modest effects on TAM. In addition to the genetic studies, the lys2ΔBgl reversion spectra of repair-proficient low and high transcription strains were obtained. In the low transcription spectrum, most of the frameshift events correspond to deletions of AT base pairs whereas in the high transcription strain, deletions of GC base pairs predominate. These results are discussed in terms of transcription and its role in DNA damage and repair.

Antimutagenic role of base-excision repair enzymes upon free radical-induced DNA damage

1998 ◽  
Vol 402 (1-2) ◽  
pp. 93-102 ◽  
Author(s):  
Jacques Laval ◽  
Juan Jurado ◽  
Murat Saparbaev ◽  
Olga Sidorkina
Keyword(s):  
Dna Damage ◽  
Free Radical ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Enzymes ◽  
Base Excision

Corrigendum to “DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion” [Biochem. Biophys. Res. Commun. 371 (2008) 225–229]

2008 ◽  
Vol 377 (1) ◽  
pp. 326
Author(s):  
Hayato Oka ◽  
Wataru Sakai ◽  
Eiichiro Sonoda ◽  
Jun Nakamura ◽  
Kenjiro Asagoshi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Gene Conversion ◽  
Dna Damage Response ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Immunoglobulin Gene ◽  
Damage Response ◽  
Base Excision

scholarly journals Dynamic Compartmentalization of Base Excision Repair Proteins in Response to Nuclear and Mitochondrial Oxidative Stress

2008 ◽  
Vol 29 (3) ◽  
pp. 794-807 ◽  
Author(s):  
Lyra M. Griffiths ◽  
Dan Swartzlander ◽  
Kellen L. Meadows ◽  
Keith D. Wilkinson ◽  
Anita H. Corbett ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Intracellular Localization ◽  
Genotoxic Stress ◽  
Mitochondrial Oxidative Stress ◽  
Base Excision

ABSTRACT DNAs harbored in both nuclei and mitochondria of eukaryotic cells are subject to continuous oxidative damage resulting from normal metabolic activities or environmental insults. Oxidative DNA damage is primarily reversed by the base excision repair (BER) pathway, initiated by N-glycosylase apurinic/apyrimidinic (AP) lyase proteins. To execute an appropriate repair response, BER components must be distributed to accommodate levels of genotoxic stress that may vary considerably between nuclei and mitochondria, depending on the growth state and stress environment of the cell. Numerous examples exist where cells respond to signals, resulting in relocalization of proteins involved in key biological transactions. To address whether such dynamic localization contributes to efficient organelle-specific DNA repair, we determined the intracellular localization of the Saccharomyces cerevisiae N-glycosylase/AP lyases, Ntg1 and Ntg2, in response to nuclear and mitochondrial oxidative stress. Fluorescence microscopy revealed that Ntg1 is differentially localized to nuclei and mitochondria, likely in response to the oxidative DNA damage status of the organelle. Sumoylation is associated with targeting of Ntg1 to nuclei containing oxidative DNA damage. These studies demonstrate that trafficking of DNA repair proteins to organelles containing high levels of oxidative DNA damage may be a central point for regulating BER in response to oxidative stress.

scholarly journals Base excision repair of oxidative DNA damage and association with cancer and aging

2008 ◽  
Vol 30 (1) ◽  
pp. 2-10 ◽  
Author(s):  
S. Maynard ◽  
S. H. Schurman ◽  
C. Harboe ◽  
N. C. de Souza-Pinto ◽  
V. A. Bohr
Keyword(s):  
Dna Damage ◽  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Base Excision

scholarly journals The Nucleotide Sequence, DNA Damage Location, and Protein Stoichiometry Influence the Base Excision Repair Outcome at CAG/CTG Repeats

Biochemistry ◽  
2012 ◽  
Vol 51 (18) ◽  
pp. 3919-3932 ◽  
Author(s):  
Agathi-Vasiliki Goula ◽  
Christopher E. Pearson ◽  
Julie Della Maria ◽  
Yvon Trottier ◽  
Alan E. Tomkinson ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nucleotide Sequence ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Ctg Repeats ◽  
Damage Location ◽  
Base Excision
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